Switching FVIII products does not pose greater immune risk: Study
Hemophilia A research focused on the risk of developing FVIII inhibitors
Switching to a different clotting factor VIII (FVIII) product was not linked to a greater risk of developing neutralizing antibodies against FVIII, or FVIII inhibitors, in people with hemophilia A, a recent study reported.
Changing treatment also had no impact on a patient’s immune profile or on therapy efficacy.
“This study contributes to reduce the concerns to switch to a different FVIII product, both in patients and their physicians,” according to researchers.
The study, “No immunological changes after factor VIII product switch: An in depth analysis in haemophilia A patients,” was published in the journal Haemophilia.
Hemophilia is caused by deficiencies in specific clotting factors — proteins that help form blood clots to prevent excessive bleeding. In hemophilia A, patients are missing FVIII.
Replacement therapy — a form of treatment in which a version of the missing clotting factor is administered to patients — is considered standard therapy in several countries.
The development of neutralizing antibodies against FVIII, a potential complication of these therapies, is driven by a lack of immune tolerance to FVIII. Potential contributing factors to this lack of immune tolerance may include the source of the delivered FVIII (either plasma-derived or recombinant, or man-made) and the use of extended half-life FVIII products, which are designed to last longer in the body.
Many patients and physicians also believe that switching products raises the probability of inhibitor development in patients treated previously with FVIII products. However, prior studies failed to confirm the existence of this association.
To address this issue, researchers at the University Medical Center Utrecht, Netherlands, analyzed data from 100 patients with hemophilia A. They switched from their current FVIII product to a recombinant standard half-life FVIII product (turoctocog alfa, sold as NovoEight), or a recombinant extended half-life FVIII product (efmoroctocog alfa, sold as Elocta in the European Union and as Eloctate in the U.S. and other countries), from 2017 to 2019.
Immune profiles assessed
Researchers evaluated if changing FVIII products led to differences in the patients’ immune profile and increased the risk of inhibitors. Changes in treatment effectiveness also were evaluated.
Patients had a median age of 39 years, and most (97%) had severe hemophilia A, corresponding to a FVIII activity less than 1%. Fifteen patients had a history of inhibitors.
Before the switch, patients used four different FVIII products: 33% used plasma-derived FVIII, and 67% used three different recombinant FVIII products. Most patients (78%) switched to NovoEight, and 22% switched to Elocta.
The median annual bleeding rate was decreased significantly in patients who switched to the recombinant extended half-life FVIII product — from three bleeds per year before the switch to one after the switch. It remained similar among those who switched between standard half-life FVIII products.
In the year after the switch, none of the patients developed inhibitors. This occurred only 1.5 years after the switch in one patient who had developed inhibitors in the past, which was considered unlikely to be related to changing treatment.
Adverse events
In 14 patients, adverse events or dissatisfaction with the new FVIII product were reported, including in 10 who switched from plasma-derived to recombinant FVIII, in two who switched between recombinant FVIII products, and in two who switched from standard half-life to the extended half-life FVIII product.
The most reported adverse event was a subjective higher bleeding tendency, although the registered annual bleeding rate did not increase significantly in these patients.
In eight patients, dissatisfaction resulted in the discontinuation of the new FVIII product. Both dissatisfaction and discontinuation were more frequent in patients who were using plasma-derived FVIII products before the switch.
Blood sample collection for immunological analysis before and after the switch was available for only 39 patients, who switched products after study approval. This group had similar age and hemophilia severity characteristics as the complete group.
Most of these patients switched between recombinant standard half-life FVIII products (51.3%), while 30.8% switched from plasma-derived to recombinant standard half-life FVIII, and 17.9% from recombinant standard half-life to extended half-life FVIII.
No remarkable changes in immunoregulatory cell functions were observed following changing treatment, regardless of the type of change, in this group. None of these patients developed FVIII inhibitors.
“In conclusion, we performed a combined immunological and clinical study to analyze the effect of FVIII product switching. Switching to a different FVIII product was not associated with differences in the immune profile or efficacy of FVIII, nor with an increased inhibitor risk,” the researchers wrote.
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